A Quality by Design Approach for Optimizing Solid Lipid Nanoparticles of Bedaquiline for Improved Product Performance.

Bedaquiline (BQ) solid lipid nanoparticles (SLNs), which have previously been formulated for parenteral administration, have a risk of patient non-compliance in treating tuberculosis. This research presents a strategy to develop BQ SLNs for oral delivery to improve patient adherence, The upper and lower levels for the formulation excipients were generated from screening experiments. Using 4 input factors (BQ, lecithin, Tween 80, and PEG), a full factorial design from 3 × 2x2 × 2 experiments was randomly arranged to investigate 3 response variables: Particle size distribution (PSD), polydispersity index (PdI), and zeta potential (ZP). High shear homogenization was used to mix the solvent and aqueous phases, with 15% sucrose as a cryoprotectant. The response variables were assessed using a zeta sizer while TEM micrographs confirmed the PSD data. Solid-state assessments were conducted using powdered X-ray diffraction and scanning electron microscopy (SEM) imaging. A comparative invitro assessment was used to determine drug release from an equivalent dose of BQ free base powder and BQ-SLN, both packed in hard gelatin capsules. The sonicated formulations obtained significant effects for PSD, PdI, and ZP. The p-values (0.0001 for PdI, 0.0091 for PSD) for BQ as an independent variable in the sonicated formulation were notably higher than those in the unsonicated formulation (0.1336 for PdI, 0.0117 for PSD). The SEM images were between 100 - 400 nm and delineated nanocrystals of BQ embedded in the lipid matrix. The SLN formulation provides higher drug levels over the drug's free base; a similarity factor (f2 = 18.3) was estimated from the dissolution profiles.

Ocular TB in Western Australia.

This was a retrospective chart review in Western Australia, Australia.To describe the diagnosis, management, and treatment outcomes of ocular TB in Western Australia (WA).This was a retrospective review of ocular TB cases in WA from 2007 to 2018 with a minimum 2-year follow-up upon completion of anti-TB therapy (ATT).A total of 44 patients were referred to WA TB clinic. Ten were excluded from the analysis of treatment response; 34 met the inclusion criteria, of whom 97.1% were born overseas. No patients had symptomatic extraocular TB. Chest X-ray showed prior pulmonary TB in 11.7% of patients (n = 4). All patients were treated with three or four ATT drugs. The most common ocular TB manifestation was retinal vasculitis (23.5%). Full resolution of ocular inflammation following ATT occurred in 66.7% (n = 22), and reduced ocular inflammation requiring only topical steroid treatment was seen in 21.2% (n = 7). Treatment failure occurred in 12.1% (n = 4). Side effects were reported in 45.6% of patients, with gastrointestinal symptoms most common (27.2%).Our study is the first Australian study examining the management of ocular TB. Our study highlights the challenges in diagnosing TB ocular disease in a low-endemicity setting and the importance of the collaboration between uveitis and TB subspecialists..

Strategies for isoniazid preventive therapy in HIV-positive patients who consume alcohol.

WHO guidance to defer isoniazid preventive therapy (IPT) among those with regular alcohol use because of hepatotoxicity concerns may exclude many people living with HIV (PLWH) at high TB risk in these settings.To evaluate hepatotoxicity during TB preventive therapy (TPT) in PLWH who report alcohol use in Uganda over 10 years.We developed a Markov model of latent TB infection, isoniazid preventive therapy (IPT - a type of TPT), and TB disease using data from the Alcohol Drinkers' Exposure to Preventive Therapy for TB (ADEPTT) study. We modeled several treatment scenarios, including no IPT, IPT with liver enzyme monitoring (AST/ALT) during treatment, and IPT with pre-screening using the tuberculin skin test (TST).The no IPT scenario had 230 TB deaths/100,000 population over 10 years, which is more than that seen in any IPT scenario. IPT, even with no monitoring, was preferred over no IPT when population TB disease incidence was >50 in 100,000.For PLWH who report alcohol use in high TB burden settings, IPT should be offered, ideally with regular AST/ALT monitoring. However, even if regular monitoring is not possible, IPT is still preferable to no IPT in almost every modeled scenario..

Bedaquiline: An Insight Into its Clinical Use in Multidrug-Resistant Pulmonary Tuberculosis.

Every year, the World Health Organization reports 500,000 new cases of drug-resistant tuberculosis (TB), which poses a serious global danger. The increased number of XDR-TB and MDR-TB cases reported worldwide necessitates the use of new therapeutic approaches. The main issues with the antitubercular medications now in use for the treatment of multidrug-resistant tuberculosis are their poor side effect profile, reduced efficacy, and antimicrobial resistance. One possible remedy for these problems is bedaquiline. The need for better treatment strategies is highlighted by the strong minimum inhibitory concentrations that bedaquiline (BDQ), a novel anti-TB medicine, exhibits against both drug-resistant and drug-susceptible TB. Bedaquiline may be able to help with these problems. Bedaquiline is a medication that is first in its class and has a distinct and particular mode of action. Bedaquiline is an ATP synthase inhibitor that is specifically directed against Mycobacterium tuberculosis and some nontuberculous mycobacteria. It is metabolized by CYP3A4. Bedaquiline preclinical investigations revealed intralesional drug biodistribution. The precise intralesional and multi-compartment pharmacokinetics of bedaquiline were obtained using PET bioimaging and high-resolution autoradiography investigations. Reduced CFU counts were observed in another investigation after a 12-week course of therapy. Meta-analyses and systematic reviews of phase II trials on bedaquiline's efficacy in treating drug-resistant tuberculosis in patients reported higher rates of cure, better culture conversion, and lower death rates when taken in conjunction with a background regimen. Here is a thorough medication profile for bedaquiline to aid medical professionals in treating individuals with tuberculosis.

A public health development intervention between acceptability and feasibility: descriptive-interpretive discussion of an example.

Introduction: the National Tuberculosis Control Program (NTP) in Cameroon participated between 2016 and 2018 in a multi-country operational study of the Union against Tuberculosis and Lung Disease (The UNION) aiming at demonstrating the efficiency and feasibility of systematic tuberculosis preventive treatment (TPT) with 3 months of an isoniazid/rifampicin (3RH) combination in under-five child contacts of bacilliferous TB patients. Cameroon was one of the participating countries of the study. Despite the promising results communicated following this study, the coverage of TPT with 3RH in Cameroon remains low. We explored the intervention under aspects of acceptability and perceived feasibility. Methods: key participants and stakeholders in this descriptive interpretative study in Cameroon were interviewed in five focus groups or individually (31 individuals). The Focus Group Discussion (FGD) and interview transcripts were analysed for different components of acceptability using a theoretical framework and the results discussed confronting them with the main objective of the study, i.e. demonstrating feasibility. Results: the children's parents expressed overall positive feelings about and acceptance of the intervention, emphasizing the unexpected empathy shown by the health staff. The involved field staff, too, showed unreserved acceptance. On the other hand, managers at the intermediate and central levels showed scepticism as to the process of initiation of the study as well as to its feasibility in the given context, neglecting aspects of resources necessary for a scaling-up and of prioritisation. Conclusion: the adoption of a public health strategy, also internationally recognized as an effective and efficient intervention, requires more than the demonstration of its acceptability or feasibility during the term of a showcase project introduced by an external development partner. Adoption is conditioned by adoption and circumspect planning involving at each stage the stakeholders on all levels of the program.

[Disseminated tuberculosis revealed by epididymal localization in an immunocompetent patient: a case report]. / Tuberculose disséminée révélée par une localisation épididymaire chez un patient immunocompétent: à propos d'un cas.

Epididymal tuberculosis is rare and often presents diagnostic difficulties. It may be indicative of a disseminated form of the infection, which is the case of our patient. A 19-year-old man, with no past medical history, was admitted for a swollen painful left scrotum that had been evolving for 8 months. He had undergone an orchiectomy and the anatomopathological examination was consistent with epididymal tuberculosis. The radiological investigations had revealed other localizations of the infection: lymphatic, pulmonary, parietal and osteoarticular tuberculosis. Anti-tuberculosis therapy was introduced. However, in the 4th month of treatment, the patient developed seizures. A cerebral magnetic resonance imaging was practiced, concluding to cerebral tuberculomas. Anti-tuberculosis treatment was continued associated to an anticonvulsant with a favourable outcome. The originality of our observation resides in the mode of revelation of a disseminated paucisymptomatic tuberculosis, by an epididymal localization, in an immunocompetent patient.

Comparison of Individual Regimen Containing Bedaquiline with Delamanid and Bedaquiline without Delamanid on Efficacy and Safety in Multidrug-resistant Tuberculosis Patients: Implementation in Dr. Soetomo General Academic Hospital, Indonesia.

BACKGROUND: Bedaquiline is one of the core drugs used to treat multidrug-resistant TB (MDR-TB). Delamanid is one of the companion drugs in group C which is used to complete the treatment regimen when drugs in groups A and B can not be used. This study was conducted to analyze the efficacy and safety between individual regimens containing bedaquiline with delamanid and bedaquiline without delamanid. METHODS: This was an observational analytic study with a retrospective design in MDR-TB patients treated with individual regimens containing bedaquiline with delamanid (bedaquiline-delamanid group) and bedaquiline without delamanid (bedaquiline group). Efficacy was measured according to the time to Acid Fast Bacilli (AFB) conversion and Mycobacterium tuberculosis culture conversion, while safety was measured specifically on QTc interval prolongation. RESULTS: The median (range) time to AFB conversion in bedaquiline-delamanid group was faster than bedaquiline group, although there was no significant difference (1.5 (1-4) months vs. 1 (1-6) months, P=0.429), the median time to culture conversion in bedaquiline-delamanid group also faster than bedaquiline group, although there was no significant difference (1 (1-6) months vs. 2 (1-6) months, P=0.089). The incidence of QTc interval prolongation in bedaquiline-delamanid group was less than bedaquiline group, although there was no significant difference (26.9% vs. 40.3%, P=0.223). CONCLUSIONS: Individual regimens containing bedaquiline with delamanid was proven to provide similar efficacy and safety profiles with individual regimens containing bedaquiline without delamanid. Delamanid should be preferred when selecting drugs to complete the treatment regimen when drugs in groups A and B can not be used.

Efficacy and safety of intrathecal dexamethasone combined with isoniazid in the treatment of tuberculous meningitis: a meta-analysis.

BACKGROUND: The treatment regimen for tuberculous meningitis (TBM) remains unclear and requires optimization. There are some reports on successful adjunct intrathecal dexamethasone and isoniazid (IDI) treatment strategies for TBM, however, there is equivocal evidence on their efficacy and safety. METHODS: A comprehensive search of English and Chinese databases was conducted from inception to February 2024. A meta-analysis was performed on randomized controlled trials (RCTs) estimating the effects of adjunct IDI on conventional anti-TB (C anti-TB) treatments or C anti-TB alone. Efficacy, adverse reaction rate, cerebrospinal fluid (CSF) leukocytes, and CSF protein were used as primary outcome indicators. CSF glucose, CSF chlorides, CSF pressure, recovery time for laboratory indicators and recovery time for clinical symptoms were used as secondary outcome indicators. RESULTS: A total of 17 studies involving 1360 (IDI group vs. C anti-TB group: 392 vs. 372; higher-dose IDI group vs. lower-dose IDI group: 319 vs. 277) patients were included in our analysis. Efficacy was significantly higher (RR 1.3, 95% CI 1.2-1.4, P < 0.001) and adverse reaction rate was significantly lower in the IDI groups (RR 0.59, 95% CI 0.37-0.92, P = 0.021). Furthermore, CSF leukocytes (WMD - 29.33, 95% CI [- 40.64 to-18.02], P < 0.001) and CSF protein (WMD - 0.79, 95%CI [-0.96 to-0.61], P < 0.001) were significantly lower in the IDI groups. Recovery time indicators were all shorter in the IDI groups, fever (SMD - 2.45, 95% CI [-3.55 to-1.35], P < 0.001), coma (SMD-3.75, 95% CI [-4.33 to-3.17], P < 0.001), and headache (SMD  - 3.06, 95% CI [- 4.05 to-2.07], P < 0.001), respectively. Higher-dose IDI was more effective than lower-dose IDI (RR 1.23, 95% CI 1.14-1.33, P < 0.001), with no significant difference in adverse reaction rate between the two (RR 0.82, 95%CI 0.43-1.56, P = 0.544). CONCLUSION: Adjunct IDI with C anti-TB can enhance therapeutic outcomes and reduce adverse reaction rate in adult TBM patients, with higher-dose IDI showing superior efficacy. These findings highlight the potential of IDI as an adjunctive therapy in TBM management. However, more high-quality RCTs from more regions should be conducted to support our results. TRIAL REGISTRATION: Retrospectively registered in PROSPERO  https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023388860 .

Lumbar Spine Infected by Mycobacterium tuberculosis and Cryptococcus neoformans: a Rare Case Report.

BACKGROUND: In July 2023, our hospital confirmed one case of lumbar spine infected complicated by Mycobacterium tuberculosis and Cryptococcus neoformans. The patient was admitted due to lower back pain for 1 year and a hard lump for 3 months. Symptoms and signs: Dressing can be seen fixed on the lower back, with severe bleeding. When the dressing is removed, a hard and protruding lump with a size of 6 cm x 8 cm, a sinus tract can be seen near the mass, with a slightly red wound and a sinus depth of about 3 cm. Light red fluid can be seen flowing out. There are no symptoms such as redness, swelling, or heat in the rest of the lower back, and the patient has no other underlying diseases or surgical history. METHODS: Lumbar magnetic resonance imaging and lumbar CT examination; Percutaneous puncture lumbar vertebral biopsy was performed, and the biopsy tissue was subjected to pathological examination, mNGS (metagenomic next-generation sequencing), and acid-fast staining; Extract pus from the lump for fungal culture and ink staining, and identify the fungi through MALDI-TOF MS. RESULTS: Bone destruction and bone marrow edema in the L5 vertebral body, compression of the spinal canal at the L5 vertebral body level; The pathological results of the biopsy tissue indicate granulomatous lesions. The acid-fast staining of the tissue is positive, and the mNGS of the tissue indicates infection with Mycobacterium tuberculosis. A single fungus was cultured from pus and identified by MALDI-TOF MS as Cryptococcus neoformans. Clinically, isoniazid 0.3 g ivgtt + rifampicin 0.45 g qd po + ethambutol 0.25 g qd po + pyrazinamide 0.75 g qd po + fluconazole 0.3 g qd po was administered for treatment. After 11 days, there was slight pain at the incision site, and the original symptoms were significantly relieved. The wound dressing was fixed in place, dry and without obvious exudation. Improved and discharged, followed up for 3 months with no recurrence of the lesion. CONCLUSIONS: mNGS is an effective identification technique that can be used to accurately diagnose suspected infection cases. MALDI-TOF MS has significant advantages over traditional detection methods in shortening detection time. This case achieved satisfactory treatment results for patients through a reasonable treatment plan, which is of great significance for exploring the diagnosis and treatment of similar disease infections.

Predictors of tuberculosis treatment outcomes among people living with HIV in some States in Nigeria.

Introduction: tuberculosis (TB) and Human Immunodeficiency Virus (HIV) remain major public health threats globally and worse when they co-exist in susceptible individuals. The study examined TB treatment outcomes and their predictive factors among people living with HIV (PLHIVs). Methods: a review of TB/HIV co-infected patients who had TB treatments across comprehensive antiretroviral therapy (ART) sites with ≥500 patients was conducted in seven United States of America President's Emergency Plan for AIDS Relief (PEPFAR)-supported States in Nigeria. Data on patient background, HIV and TB care, and TB treatment outcomes were collected using an Excel abstraction template. The data was analyzed using SPSS and an association was examined using a chi-square test while binary logistic regression was used to determine predictors of TB treatment outcomes (P< 0.05). Results: two thousand six hundred and fifty-two co-infected patients participated in the study. The mean age of participants was 37 ± 14 years. A majority had TB treatment success (cured = 1059 (39.9%), completed = 1186 (44.7%)). Participants who had pulmonary TB, virally suppressed and commenced isoniazid (INH) before TB diagnosis were more likely to have a favorable TB treatment outcome compared to those who had extrapulmonary TB (AOR = 7.110, 95% CI = 1.506 - 33.565), virally unsuppressed (AOR = 1.677, 95% CI = 1.036 - 2.716) or did not commence INH before TB diagnosis (AOR = 1.486, 95% CI = 1.047 - 2.109). Conclusion: site of infection, immune status, exposure to ART, and INH prophylaxis were found to predict TB treatment outcomes among PLHIVs. Stakeholders should ensure early commencement of ART and INH prophylaxis for PLHIVs.

Impact of line probe assay-based molecular testing on individualized treatment in patients with rifampicin-resistant tuberculosis: data from the prospective INNOVA4TB cohort study in Ukraine.

BACKGROUND: Ukraine remains a high World Health Organization priority country for drug-resistant tuberculosis (TB). Rifampicin-resistant TB (RR-TB) has a more protracted, more complicated, and more expensive treatment. In 2021, Ukraine reported 4025 RR-TB cases - 5.4 times more (751) than all 30 European Union/ European Economic Area countries together. OBJECTIVES: The objective of the study was to determine the diagnostic accuracy of line probe assay (LPA), AID Autoimmun Diagnostika GmbH, for detecting resistance to anti-TB drugs and its clinical application for selecting treatment regimens. DESIGN: A prospective observational cohort study. METHODS: From May 2019 to June 2020, we consecutively enrolled patients with active TB hospitalized at the Regional Phthisiopulmonology Center (Vinnytsia, Ukraine), aged between 18 and 82 years. The LPA was performed in the Genetic Research Laboratory at National Pirogov Memorial Medical University, Vinnytsia, Ukraine. RESULTS: A total of 84 clinical specimens and 97 culture isolates from 126 TB patients were tested during the study. Accuracy (95% confidence interval) of LPA for clinical samples in comparison with phenotypic drug susceptibility test (DST) was 80.1 (68.5-89.0) for isoniazid (H), 74.7 (62.4-84.6) for rifampicin (R), 74.4 (62.5-84.1) for ethambutol, 71.4 (41.9-91.6) for streptomycin, 84.6 (62.4-96.5) for prothionamide/ethionamide, and 84.6 (73.6-92.3) for levofloxacin (Lfx), respectively. We found a significantly higher sensitivity of LPA for H, R, and Lfx for the culture isolates compared to clinical specimens (p < 0.05). LPA detected different mutations in 6 out of 17 (35.5%) patients susceptible to R by Xpert. A shorter treatment regimen with an injectable agent demonstrated a low suitability rate of 5% (8/156) in a cohort of RR-TB patients from Ukraine. CONCLUSION: Initial LPA testing accurately identifies resistance to anti-TB drugs and facilitates the selection of an appropriate treatment regimen, minimizing exposure to empirical therapy.

Study about the impact of rapid resistance detection on the treatment of patients with tuberculosis in Ukraine written by healthcare and biomedical professionals to better understand how we can improve the results of treatment and to prevent spreading of resistant bacteriaWhy was the study done? Ukraine has over 4000 patients with tuberculosis (TB) resistant to at least one drug (rifampicin) - five times that of all 30 European Union/European Economic Area countries combined. Unfortunately, only about 60% of such patients have been successfully treated in 2019. At that time, the majority of people suffering from tuberculosis in Ukraine, after checking resistance to rifampicin, initially received standard combinations of the first-line or second-line anti-TB medicines before the result of traditionally used tests (usually few weeks later) became available to individualize the treatment. Alternatively, the sputum could be transported to some overloaded reference laboratories located hundreds of km away from the treatment places.What did the researchers do? The INNOVA4TB team implemented rapid diagnostics of drug resistance in routine practice, guiding key antibiotics use in TB patients. A total of 181 samples from 126 individuals were tested during 2019-2020.What did the researchers find? This new diagnostic technology accurately detected resistance to 9 anti-TB drugs in sputum samples. It could be helpful to select appropriate TB treatment regimens, reducing time for decision from 1 month up to 2 days. Recommended at the study time 9-month shorter standardized treatment regimen with injectable agent was suitable only for 5% of patients for whom it was indicated in Vinnytsia region of Ukraine.What do the findings mean? The study has demonstrated successful implementation of the new molecular diagnostic technology from scratch in a country with restricted resources and limited TB laboratory capacity. This test can facilitate optimal distribution of available wards among patients with different profiles of resistance and correct choice between treatment options.

Shedding light on vitamin D in tuberculosis: A comprehensive review of clinical trials and discrepancies.

Over the past few decades, there has been extensive research on the use of vitamin D as an adjunctive therapy in the treatment and prevention of tuberculosis. In vitro studies have provided valuable insights into the mechanisms by which vitamin D activates the immune response to combat Mycobacterium tuberculosis. These encouraging findings have spurred clinical investigations globally to assess the effectiveness of vitamin D as a preventive measure and as an adjunctive treatment for tuberculosis. However, the results from these clinical studies have been contradictory, with some demonstrating clear efficacy while others report only modest or no activity. In this review, we aim to analyze the clinical studies on vitamin D and examine the possible discrepancies observed in their outcomes.

Digital Adherence Technologies Linked to Mobile Money Incentives for Medication Adherence Among People Living With Tuberculosis: Mixed Methods Feasibility and Acceptability Study.

BACKGROUND: Complementing digital adherence technologies (DATs) with mobile money incentives may improve their utility in supporting tuberculosis medication adherence, yet the feasibility and acceptability of this integrated approach remain unclear. OBJECTIVE: This study aims to describe the feasibility and acceptability of a novel DAT intervention called My Mobile Wallet composed of real-time adherence monitoring, SMS text message reminders, and mobile money incentives for tuberculosis medication adherence in a low-income setting. METHODS: We purposively recruited people living with tuberculosis from the Mbarara Regional Referral Hospital in Mbarara, Uganda, who (1) were starting tuberculosis treatment at enrollment or within the past 4 weeks, (2) owned a mobile phone, (3) were able to use SMS test messaging, (4) were aged ≥18 years, and (5) were living in Mbarara district. At study exit (month 6), we used interviews and questionnaires informed by the unified theory of acceptance and use of technology (UTAUT) to collect feasibility and acceptability data, reflecting patients' experiences of using each component of My Mobile Wallet. Feasibility also included tracking the functionality of the adherence monitor (ie, an electronic pillbox) as well as SMS text message and mobile money delivery. We used a content analytical approach to inductively analyze qualitative data and Stata (version 13; StataCorp LLC) to analyze quantitative data. RESULTS: All 39 participants reported that the intervention was feasible because it was easy for them to use (eg, access and read SMS text messages) and worked as expected. Almost all SMS text messages (6880/7064, 97.4%) were sent as planned. The transmission of adherence data from the monitor worked well, with 98.37% (5682/5776) of the data transmitted as planned. All participants additionally reported that the intervention was acceptable because it helped them take their tuberculosis medication as prescribed; the mobile money incentives relieved them of tuberculosis-related financial burdens; SMS text message reminders and electronic pillbox-based alarms reminded them to take their medication on time; and participants perceived real-time adherence monitoring as "being watched" while taking their medication, which encouraged them to take their medication on time to demonstrate their commitment. The intervention was perceived as a sign of care, which eventually created emotional support and a sense of connectedness to health care. Participants preferred daily SMS text message reminders (32/39, 82%) to reminders linked to missed doses (7/39, 18%), citing the fact that tuberculosis medication is taken daily. CONCLUSIONS: The use of real-time adherence monitoring linked to SMS text message reminders and mobile money incentives for tuberculosis medication adherence was feasible and acceptable in a low-resource setting where poverty-based structural barriers heavily constrain tuberculosis treatment and care.

Pharmacokinetics of standard versus high-dose rifampin for tuberculosis preventive treatment: A sub-study of the 2R2 randomized controlled trial.

BACKGROUND: Pharmacokinetic data of rifampin, when used for tuberculosis preventive treatment (TPT) are not available. We aimed to describe the pharmacokinetics of rifampin used for TPT, at standard and higher doses, and to assess predictors of rifampin exposure. METHODS: A pharmacokinetic sub-study was performed in Bandung, Indonesia among participants in the 2R2 randomized trial, which compared TPT regimens of 2 months of high-dose rifampin at 20 mg/kg/day (2R20) and 30 mg/kg/day (2R30), with 4 months of standard-dose rifampin at 10 mg/kg/day (4R10) in adolescents and adults. Intensive pharmacokinetic sampling was performed after 2-8 weeks of treatment. Pharmacokinetic parameters were assessed non-compartmentally. Total exposure (AUC0-24) and peak concentration (Cmax) between arms were compared using one-way ANOVA and Tukey's post-hoc tests. Multivariable linear regression analyses were used to assess predictors of AUC0-24 and Cmax. RESULTS: We enrolled 51 participants in this study. In the 4R10, 2R20, and 2R30 arms, the geometric mean AUC0-24 was 68.0, 186.8, and 289.9 h⋅mg/L, and Cmax was 18.4, 36.7, and 54.4 mg/L, respectively; high interindividual variabilities were observed. Compared with the 4R10 arm, AUC0-24 and Cmax were significantly higher in the 2R20 and 2R30 arms (P < 0.001). Drug doses, body weight, and female sex were predictors of higher rifampin AUC0-24 and Cmax (P < 0.05). AUC0-24 and Cmax values were much higher than those previously reported in persons with TB disease. CONCLUSIONS: Doubling and tripling the rifampin dose led to three- and four-fold higher exposure compared to standard dose. Pharmacokinetic/pharmacodynamic modelling and simulations are warranted to support trials of shortening the duration of TPT regimens with high-dose rifampin.

Tuberculosis preventive treatment uptake among people living with HIV during COVID-19 period in Addis Ababa, Ethiopia: a retrospective data review.

BACKGROUND: Screening for tuberculosis (TB) and providing TB preventive treatment (TPT) along with antiretroviral therapy is key components of human immune deficiency virus (HIV) care. The uptake of TPT during the coronavirus disease 2019 (COVID-19) period has not been adequately assessed in Addis Ababa City Administration. This study aimed at assessing TPT uptake status among People living with HIV (PLHIV) newly initiated on antiretroviral therapy during the COVID-19 period at all public hospitals of Addis Ababa City Administration, Ethiopia. METHODS: A retrospective data review was conducted from April-July 2022. Routine District Health Information System 2 database was reviewed for the period from April 2020-March 2022. Proportion and mean with standard deviation were computed. Logistic regression analysis was conducted to assess factors associated with TPT completion. A p-value of < 0.05 was considered statistically significant. RESULTS: A total of 1,069 PLHIV, aged 18 years and above were newly initiated on antiretroviral therapy, and of these 1,059 (99.1%) underwent screening for TB symptoms. Nine hundred twelve (86.1%) were negative for TB symptoms. Overall, 78.8% (719) of cases who were negative for TB symptoms were initiated on TPT, and of these 70.5% and 22.8% were completed and discontinued TPT, respectively. Of 719 cases who were initiated on TPT, 334 (46.5%) and 385 (53.5%) were initiated on isoniazid plus rifapentine weekly for three months and Isoniazid preventive therapy daily for six months, respectively. PLHIV who were initiated on isoniazid plus rifapentine weekly for three months were more likely to complete TPT (adjusted odds ratio [AOR],1.68; 95% confidence interval [CI], 1.01, 2.79) compared to those who were initiated on Isoniazid preventive therapy daily for six months. CONCLUSION: While the proportion of PLHIV screened for TB was high, TPT uptake was low and far below the national target of achieving 90% TPT coverage. Overall a considerable proportion of cases discontinued TPT in this study. Further strengthening of the programmatic management of latent TB infection among PLHIV is needed. Therefore, efforts should be made by the Addis Ababa City Administration Health Bureau authorities and program managers to strengthen the initiation and completion of TPT among PLHIV in public hospitals.